Faulty fountains of youth: adult stem cells may contribute to aging

Science News,  Feb 9, 2008  by Patrick Barry

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Skin sags. Hair grays. Organs don't work quite like they used to. A gradual wearing out and running down of the body's tissues seems an inherent part of growing older. Rejuvenation of skin, muscles, and other body parts naturally declines with the passing years.

Scientifically speaking, however, this observation is much less self-evident. Some cells in a person's body can resist the tide of aging. Consider the reproductive cells a person carries that will become the cells of newborn children who have 80-plus years of life to look forward to. Generation after generation, these reproductive cells form an unbroken line stretching for millennia.

The reason that an otherwise healthy person grows old and dies remains a mystery. Scientists have suggested several suspects for why people's bodies wear out with age, including accumulated damage to DNA, free radicals, and the shortening of telomeres--the caps on the ends of chromosomes. While each of these factors may play a part, biologists acknowledge that their understanding of aging is incomplete.

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Enter stem cells. Scientists have long known that people have small reservoirs of stem cells in some of their tissues, such as bone marrow. These stem cells are distinct from those found in newly fertilized embryos--the more controversial embryonic stem cells. The embryonic type can become any type of cell in the body.

Adult stem cells, in contrast, can normally generate new cells only for the tissue in which they're found: blood cells for blood, intestinal cells for the intestines. As old cells in these tissues are damaged or wear out, nearby stem cells can manufacture new ones to take their place. At the same time, the stem cells produce more copies of themselves, maintaining a seemingly indefinite pool of cells capable of churning out a stream of replacement cells.

Until recently, most scientists thought that adult stem cells existed only in tissues that need to constantly replace their cells, such as skin, blood, and the lining of the intestine. But over the past few years, researchers have found stem cells in many, perhaps most, of the body's organs and tissues. Even the brain, which scientists once thought never replaced its nerve cells during adulthood, is now known to have stem cells that make new nerve cells throughout life (SN: 6/16/07, p. 376).

With the realization that so much of the body contains self-renewing stem cells, scientists began wondering whether changes in these stem cells over time might contribute to aging.

Imagine that, as a person ages, these fountains of cellular youth might start to run dry. As the supply of fresh cells dwindles, tissues would gradually decline and show signs of age. "That was the initial model" of how stem cells could be involved in aging, says Norman E. Sharpless, a stem cell expert at the University of North Carolina in Chapel Hill. And some data support this idea.

Graying of hair, for example, could be caused by a decline in melanocyte stem cells that accompanies aging, as observed by Emi K. Nishimura and her colleagues at Dana-Farber Cancer Institute in Boston. Melanocytes make the hair pigment melanin, so depleting these stem cells eventually causes loss of hair color, the team reported in Science in 2005.

Elderly people also have diminished resistance to disease because their immune systems make fewer of the disease-fighting white blood cells known as lymphocytes. In mice, bone marrow stem cells produce fewer lymphocytes as the mice get older, Derrick J. Rossi, now at Harvard Stem Cell Institute in Cambridge, reported in 2005 in the Proceedings of the National Academy of Sciences.

Yet evidence is mounting that the connection between adult stem cells and aging is more complex. Some kinds of stem cell actually grow more abundant with age. And just as stem cells affect aging, the aging body affects stem cells.

TINKERING WITH TIME To untangle these effects, scientists led by Thomas A. Rando of Stanford University surgically joined pairs of mice like reconnected Siamese twins. The team linked the animals' circulatory systems so that blood from each member of a pair flowed through both mice. One mouse in each pair was old; the other was young.

Scientists knew that the ability of muscle stem cells (also called satellite cells) to repair damaged muscles declines substantially with age. Rando's team wanted to find out whether such declines should be attributed to changes in the satellite cells themselves or to changes in the cells' environment as the animals aged.

"There clearly is an effect of aging on stem cells," Rando says. "But I think the other question is ... are those changes reversible or irreversible?"

Amazingly, the blood of the young mice completely restored the tissue-healing powers of the satellite cells in the older mice, Rando's team reported in 2005 in Nature. Exposure to the young blood reactivated a system of proteins inside the cells called the Notch signaling pathway, which is crucial for triggering the cells' muscle-repair functions. Notch signaling in satellite cells normally declines in old age, but Rando's experiment showed that this decline is a response to changes in the blood, not the result of an inherent wearing out of the satellite cells themselves.